1. Field of the Invention
The present invention relates to feed additives for fattening pigs and lactating sows which contain a reduced form of folic acid as an active ingredient, increase the amount of a reduced form of folic acid in the plasma of fattening pigs, and improve the fattening efficiency of fattening pigs; and to a feed for fattening pigs and lactating sows which contains such a feed additive. The present method also relates to a method of fattening pigs by feeding pigs such a feed additive or feed.
2. Discussion of the Background
Folic acid is a coenzyme participating in the synthesis of amino acids, such as methionine, serine, and glutamic acid, and purine bases of the nucleic acids which constitute DNA. It has been confirmed by epidemiological surveys on pregnant women and tests on pregnant guinea pigs that the demand for folic acid increases and its concentration in blood plasma decreases in mother's bodies during pregnancy (Pritchard J. A. et al., Am. J. Obst. Gynecol., Vol. 104, p. 388 (1969) and Habibzadeh H. C. et al., Br. J. Nutr., Vol. 55, p.23 (1986)).
It has also been confirmed with regard to domestic pigs, that the amount of reduced forms of folio acid in the blood plasma of sows decreases during pregnancy (Natsuhori et al., Final Program and Abstracts Book of the 10th International Symposium: "Chemistry and Biology of Pteridines and Folates," p.196 (1993)). It has also been proven that breeding efficiency can be improved by administering folic acid (an oxidized form) to pregnant pigs by means of intramuscular injection (Matte J. J. et al., J, Anim. Sci., Vol. 67 p. 426 (1989) and Friendship R. M. et al., Can. Vet. J., Vol. 32, p.564 (1991)), which shows the importance of administering folic acids to pregnant pigs (sows).
Meanwhile, there has been only little study regarding the influence which folic acid has on fattening pigs for meat in terms of fattening efficiency. In one study conducted by J. J. Matte, et al., the level of folic acid (in an oxidized form) in the plasma was found to increase by intramuscularly injecting folic acid to fattening pigs every week without a change in the weight increase, and the feed efficiency tended to improve (Reprod. Nutr. Dev., vol. 30, pp. 103-114 (1990)). In the other study conducted by J. J. Matte, et al., it was reported that when folic acid (in an oxidized form) is intramuscularly injected in lactating sows, the level of folic acid in breast milk and in the plasma of suckling baby pigs increases but no influence is found in terms of weight increase (J. Anim, Sci., vol. 67, pp. 426-431 (1989)).
In general, folic acid is chemically synthesized. Chemically synthesized folic acid is of an oxidized form, and an oxidized form of folic acid per se does not function as a coenzyme. Usually, after being absorbed into the body, it is transformed by dihydrofolic acid dehydrogenase into 7,8-dihydrofolic acid (H.sub.2 folic acid), which is then enzymatically reduced to reduced forms of folic acid such as tetrahydrofolic acid (THF) or 5-methyltetrahydrofolic acid (5 MF) which act as coenzymes. Therefore, the effect of the administration of folic acids can be determined by measuring the amount of THF or 5 MF in the blood plasma. However, it is not possible to determine the amount of the reduced forms of folic acid alone in a selective manner by the known determination method since it is based on the radioligand technique, and hence it is not possible to obtain an accurate value of the amount of the reduced forms of folic acid contained in the blood plasma. In the present specification, the reduced forms of folic acid may also be referred to as "active-type folic acids" since they have physiological activities, and the oxidized forms of folic acid may also be referred to as "inactive-type folic acids" since they have no physiological activities.
For the purpose of analyzing the effects of administering folic acids to pigs, the HPLC-ECD method has been developed recently for determining the content of the active-type folic acids in the blood plasma by high performance liquid chromatography using an electrochemical detector, and, by using this method, investigations have been made on the extent of appearance of THF and 5 MF in blood plasma at the time when folic acid (an oxidized form) is administered to pigs by intravenous injection, intramuscular injection or oral administration. To be more specific, 4 grown-up pigs having a body weight of around 25 kg were distributed according to the Latin square method to 4 factors: intravenous injection (1 mg/kg of body weight), intramuscular injection (1 mg/kg of body weight), small dosage oral administration (1 mg/kg of body weight) and large dosage oral administration (50 mg/kg of body weight), of folic acid (in an oxidized form), and tests were performed. As a result, the concentration of THF and 5 MF in the blood plasma increased in the cases of intravenous injection, intramuscular injection and large dosage oral administration. Accordingly, it is considered that the administered folic acid (an oxidized form) was adsorbed and converted to active-type folic acids in the liver, etc. On the other hand, THF and 5 MF did not appear in the blood plasma in the case of small dosage oral administration. With regard to the above, see Eiichi Kokue et al., "Abstract Book of the 113th Convention of Japan Veterinary Society," p. 112 (1992). In rats, it has been known that the concentration of reduced forms of folic acid increase rapidly even when an oxidized form of folic acid is administered in a small dosage (Tsunematu K. et al., Cong. Anom., Vol. 30, p. 113 (1990)).
From the above, it is considered that pigs possess a capability of converting inactive-type folic acids to active-type folic acids, but their capability of absorbing inactive-type folic acids from the digestive tract is far less than rats. It has also been found that an extremely large quantity of inactive-type folic acids must be administered to pigs in order to increase the amount of active-type folic acids in the blood plasma by oral administration of inactive-type folic acids.
Thus, there remains a need for feed additives for fattening pigs which increase the amount of reduced forms of folic acid in the plasma and which improve the efficiency of fattening pigs, feeds for fattening pigs which contain such an additive, and a method of fattening pigs by feeding pigs or lactating sows such a feed additive or feed.